The proposed research continues previous studes directed at two principal objectives. One is to understand the structual basis of acetylcholine receptor function. The second is to understand pathological mecanisms involved in the disease myasthenia gravis. Receptor protein purified from both electric organs and muscle will be studied. The polypeptide chains composing electric organ receptor have been purified and are being characterized. Antibodies to purified receptor and its component peptides are being used to determine structural similarities between receptors from various sources. These antisera are also being used to alter receptor metabolism and function. These studies will be extended and refined by using antisera to defined parts of these polypeptide chains and by preparing monoclonal antibodies of known specificity for parts of the receptor molecule. These antibodies will be used to probe purified receptors as well as receptors in membrane fragments, cells, and intact animals. Reconstitution of receptor into artificial planar lipid bilayers and vesicles is being investigated. Esperimental autoimmune myasthenia gravis (EAMG) induced by immunizing animals with purified receptor is bein studied as a model for human MG. Our previous and current studies are providing a general understanding of the pathological mechanisms leading to impaired neuromuscular transmission in EAMG and MG. The proposed studies are directed at studying three processes: 1) the initiation of the immune response to receptor, 2) detailed mechanisms by which transmission is impaired, and 3) methos by which the immune response to receptor can be controlled. Sera and muscle from patients with MG are being studied in parallel with specimens from the animal model. Attempts are being made to identify previously unrecognized diseases phenotypically similar to MG but not caused by an autoimmune response to receptor.